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Iridium-catalysed arylation of C–H bonds enabled by oxidatively induced reductive elimination

Nature Chemistry volume 10, pages 218–224 (2018)Cite this article

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Abstract

Direct arylation of C–H bonds is in principle a powerful way of preparing value-added molecules that contain carbon–aryl fragments. Unfortunately, currently available synthetic methods are not sufficiently effective to be practical alternatives to conventional cross-coupling reactions. We propose that the main problem lies in the late portion of the catalytic cycle where reductive elimination gives the desired carbon–aryl bond. Accordingly, we have developed a strategy where the Ir(III) centre of the key intermediate is first oxidized to Ir(IV). Density functional theory calculations indicate that the barrier to reductive elimination is reduced by nearly 19 kcal mol–1 for this oxidized complex compared with that of its Ir(III) counterpart. Various experiments confirm this prediction, affording a new methodology capable of directly arylating C–H bonds at room temperature with a broad substrate scope and in good yields. This work highlights how the oxidation states of intermediates can be targeted deliberately to catalyse an otherwise impossible reaction.

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Figure 1: Schematic representation of C–H arylation reactions with aryl nucleophiles catalysed by transition-metal complexes.
Figure 2: Mechanistic studies on the transmetallation and oxidatively induced carbon–aryl bond-forming step of the present arylation.
Figure 3: Calculated energy profiles for the reductive elimination from Ir(III)–aryl, Ir(IV)–aryl and Ir(V)–aryl intermediates.
Figure 4: Detailed mechanistic studies on the oxidation and reductive elimination step of the present iridium-catalysed C−H arylation.
Figure 5: Proposed catalytic cycle of the present Ir(III)-catalysed C–H arylation.

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Change history

  • 13 February 2018

    In the version of this Article originally published, the oxidation states of the iridium centres in figures 2, 4 and 5 were formatted incorrectly. These have been corrected after print.

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Acknowledgements

This research was supported by the Institute for Basic Science (IBS-R010-D1) in Korea.

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Authors and Affiliations

  1. Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea

    Kwangmin Shin, Yoonsu Park, Mu-Hyun Baik & Sukbok Chang

  2. Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon, 34141, Republic of Korea

    Kwangmin Shin, Yoonsu Park, Mu-Hyun Baik & Sukbok Chang

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  1. Kwangmin Shin
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Contributions

K.S., Y.P., M.-H.B. and S.C. conceived and designed the project and wrote the manuscript. K.S. and Y.P. carried out the experiments. Y.P. performed DFT calculations. S.C. organized the research. All authors analysed the data, discussed the results and commented on the manuscript.

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Correspondence to Mu-Hyun Baik or Sukbok Chang.

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Shin, K., Park, Y., Baik, MH. et al. Iridium-catalysed arylation of C–H bonds enabled by oxidatively induced reductive elimination. Nature Chem 10, 218–224 (2018). https://doi.org/10.1038/nchem.2900

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